This Funding Opportunity Announcement (FOA) solicits
applications that propose to conduct time-sensitive ancillary studies related
to the NIAMS mission in conjunction with privately or publicly funded, large,
ongoing clinical projects. The ongoing “parent” project can be a large
clinical trial or observational study, or a disease registry that can provide
a sufficient cohort of well-characterized patients, infrastructure, data, and
biological samples. Applications submitted in response to this FOA will
undergo an accelerated review and award process. Each application must
include a timeline to demonstrate that the parent project has adequate time
left to accommodate the proposed ancillary study. In addition, it must
justify the time-sensitive nature of the ancillary study and the need for an
expedited review and award process. It must also document permission from the
parent project to use the patient cohorts, data, and biological materials.
The objective of this FOA is to provide a flexible mechanism to leverage
established resources and maximize the return on existing investments in
parent projects. Successful ancillary studies will enhance the scientific
content and value of the parent projects, improve the research community’s
understanding of a disease or organ system in the NIAMS portfolio, and thus
identify novel targets for diagnosis, treatment, and prevention of
disease.

Key Dates

Posted Date

July 20, 2012

Open Date (Earliest Submission Date)

November 3, 2012

Letter of Intent Due Date

November 3, 2012; March 15, 2013

Application Due Date(s)

December 3, 2012; April 16, 2013, by 5:00 PM local time of
applicant organization.

AIDS Application Due Date(s)

December 3, 2012; April 16, 2013, by 5:00 PM local time of
applicant organization.

Scientific Merit Review

February/March 2013; June/July 2013

Advisory Council Review

May 2013; August 2013

Earliest Start Date(s)

May 2013; September 2013

Expiration Date

April 17, 2013

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in
the SF
424 (R&R) Application Guide, except where instructed to do otherwise
(in this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

Clinical studies, whether clinical trials, observational
studies, or disease registries, often represent a substantial financial
commitment from the sponsors and enormous effort from the investigators who
establish an infrastructure for patient recruitment, examination, and
follow-up. These large clinical projects, particularly clinical trials, offer
unique experimental windows to human disease that are largely under-exploited.
Additional studies that go beyond the core activities of the original clinical
project can explore the research opportunities offered in the established
cohorts and generate new information to enhance the scientific content of the
original project. Such studies that are not part of the original parent project
are referred to as ancillary studies.

Objectives

This FOA solicits grant applications that propose to conduct
studies ancillary to privately or publicly funded, large, ongoing clinical
projects. These large, ongoing, parent projects can be clinical trials,
observational studies, or disease registries that can provide sufficient
cohorts of well-characterized patients, infrastructure, data, and biological
samples. The parent projects must be independently funded by the NIAMS, other
NIH institutes or government agencies, or private sponsors; they will not
receive support from this FOA. Unlike those of the ancillary studies, the
objectives of the parent study need not relate to the NIAMS mission, so long as
the parent study provides an appropriate venue for the proposed ancillary
study. Information about clinical trials currently supported by a variety of
public and private entities can be obtained from http://www.clinicaltrials.gov/.

The ancillary studies supported under this FOA should focus
on areas that are not studied in the parent project and address new research
questions that are related to the mission of NIAMS (http://www.niams.nih.gov/About_Us/Mission_and_Purpose/mission.asp)
in the venue of a parent project. The parent project can provide existing
resources to facilitate the research and make it more efficient than initiating
the same research de novo.

The following are examples of research that might be
proposed under this FOA. These are only examples and are not meant to be
inclusive:

Basic physiologic, cellular, and genetic mechanisms of disease.

Underlying mechanism of action of a drug or intervention.

Biomarkers discovery and validation.

Quality of life and patient education materials.

Economic implications of a disease and its treatment.

Development of new statistical methodology to enhance the parent
study design or analysis of data.

Evaluation of patient-reported outcomes using novel technologies.

Ancillary studies must document permission from the parent
project to use the patient cohorts, data, and biological materials. Ancillary
studies must not interfere with the parent project or unduly burden
participants. Applicants must document that proper informed consent to conduct
ancillary studies has been or will be obtained, and must agree to follow the
procedures and policies established by the parent project. Ancillary studies
may involve the entire cohort of participants in a parent study or selected
subsets, depending on the scientific questions posed and the sample size
required to answer them. The ancillary studies may also draw patients from two
or more parent projects if they are able to obtain approval from these parent
projects and if their research plan is feasible. In general, this FOA will not
support the recruitment of patients who are not already enrolled in the parent
study or studies; however, recruitment of a small number of normal controls is
acceptable provided that the cost is minimal (e.g., no more than one budget
module).

Once a parent project clinical protocol is finalized, its
investigators often are ready to begin recruiting patients as soon as they
obtain Institutional Review Board approval. This time-sensitive feature demands
a robust administrative system within NIAMS that is compatible with the
timeline of the parent project to avoid any missed research opportunities; an
accelerated review and award process would allow the initiation of ancillary
studies in a timely fashion to take advantage of the unique resources and
well-characterized cohorts being established in the parent project. Applications
submitted to this FOA will be subject to an accelerated peer review and award
process.

An ancillary study may begin any time during the course of
the parent project, but ideally should begin in the early stages of the parent
project, and before recruitment in completed. Each application must include a
timeline to demonstrate that the parent project has adequate time left to carry
out the proposed ancillary study. Each application must justify the
time-sensitive nature of the ancillary study and clearly explain on a separate
and clearly identifiable paragraph titled "Time-Sensitivity
Justification" why an expedited review and award process is essential to
its feasibility. This information will be disclosed in the approach of the
Research Strategy section of the application.

Examples of characteristics that would support the case for
time-sensitivity include (1) the need for support to collect samples or data
prior to end of recruitment, (2) the need to perform analysis on
soon-to-be-collected fresh specimens, or (3) the need for collecting
post-intervention data from research participants in a trial that will end. If
the proposed research does not need to be concurrent with the parent project
(e.g., secondary analysis of existing datasets); or is a sample collection that
is already part of the parent study; or a data collection by the parent study
is completed before the beginning of the ancillary study, then the application
will be considered non-responsive to this FOA, unless the existing data set has
to be analyzed at the same time with soon-to-be-collected samples.

Applicants will have to carefully justify this case and any
other time-sensitivity rationale in the Research Approach Section. Investigators
who could complete the same work using the standard application process should
not apply to this FOA.

This FOA encourages collaboration between basic and clinical
investigators and partnership with private entities. In addition, this FOA
encourages junior investigators to take a leading role in clinical research
with the support and collaboration of senior investigators. The prospective
applicants are not necessarily investigators in the parent study. However,
collaborations in which a senior investigator from the parent study mentors a
junior investigator on an ancillary study are encouraged.

The OER
Glossary and the SF 424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The NIAMS intends to commit approximately
$1.5 million total costs in FY2013 to support a
total of four to six new awards combined from the two companion FOAs for R01s (RFA-AR-13-010) and R21s (RFA-AR-13-011).
Awards issued under this FOA are contingent upon the availability of funds
and the submission of a sufficient number of meritorious applications.

Award Budget

Budgets for direct costs of up to $250,000 per year and a
project duration for up to four years may be requested.

Award Project Period

A duration for up to four years may be requested.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications
from the SF 424 (R&R) Application Guide.

All ancillary study applications MUST
include a letter or statement from one of the parent study leadership
committees (i.e., Steering Committee, Scientific Advisory Board, Data and Safety
Monitoring Board or Observational Study Monitoring Board, or other equivalent
oversight committees) documenting its approval of the proposed ancillary study.
This letter of approval must explicitly indicate that the required patients,
samples, data, and materials from the parent project are accessible to the
ancillary study. The letter should also provide the details of any agreement
reached between the parent and ancillary study if there are requirements for
limited data access and distribution. It must provide assurance that there is
adequate time left in the parent study to carry out the ancillary study. This
letter should be included as an upload in Item 14 of the PHS398 Components
Letters of Support. Applications missing such documentation will be considered
non-responsive to this FOA. Applications in which the critical time lines for
the parent study and ancillary study are incompatible or ambiguous may not be
reviewed.

All ancillary study applications must include a paragraph
with the heading "Time-Sensitivity Justification" under Approach to
explicitly justify the time-sensitive nature of the proposed ancillary study.
The intent of this FOA is to fund scientifically meritorious applications that
demonstrate the need for expedited review and award in order to complete the
proposed work. Applications that do not demonstrate the need for accelerated
review and award are encouraged to submit through the regular NIH submission
process. (http://grants.nih.gov/grants/guide/pa-files/PA-11-260.html)

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
submission of applications for this FOA. Follow all instructions in the SF424
(R&R) Application Guide to ensure you complete all appropriate “optional”
components.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Research Strategy

In Significance, the applicant should also include an explanation
of why the proposed ancillary studies need the cohorts recruited in the
identified parent project, as opposed to similar subjects not participating in
the parent project, or, in the case of statistical methodology, how the parent
study would especially benefit from the new methodology.

In Approach, the applicant should include methods of data
analysis and power calculations, as well as a justification for the required
sample size. A restatement of the sample size calculations from the parent
clinical trial is insufficient. The plan must also include a discussion of the
statistical procedures that will be used to analyze the data. It is strongly
recommended that a statistician be part of the research team and active in
preparation of the application.

Protection of Human Subjects

In Protection of Human Subjects all procedures to protect the
subjects' privacy rights must be clearly described. In addition, documentation
of the burden to the patients enrolled in the ancillary application must be
provided. IRB approval is not required at the time of submission for the
ancillary study protocol and related documents. Successful applicants will be
required to submit this information at the time of award. NIH will treat as
confidential any scientific, preclinical, clinical, or formulation data and
information that the sponsor deems to be proprietary.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Appendix

Do not use the Appendix to circumvent page limits. Follow
all instructions for the Appendix as described in the SF424 (R&R)
Application Guide, with the following modification:

·
The clinical protocol of the parent project may be submitted as
appendix materials.

Foreign Institutions

Foreign (non-US) institutions must follow policies described
in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in
advance of the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure accurate
and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the SF
424(R&R) Application Package. Failure to register in the Commons and
to include a valid PD/PI Commons ID in the credential field will prevent the
successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional
information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by NIAMS, NIH. Applications that are
incomplete and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to
notify the NIAMS Referral Office by email at linh1@mail.nih.gov when the application has been submitted. Please include the FOA number and
title, PD/PI name, and title of the application.

Post Submission Materials

Due to the expedited review time, no
post submission materials are permitted.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in
consideration of the following review criteria and additional review criteria
(as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field? Does the proposed ancillary study enhance
the scientific content and value of the parent project(s)?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD(s)/PI(s), do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project? Does the application describe how the PD(s)/PI(s) of the ancillary study and the parent
project interact on a regular basis and work cooperatively to ensure the
successful completion of the ancillary study while maintaining the integrity of
the parent project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Time Sensitivity Justification

The committee will evaluate the adequacy of the
justification for time-sensitivity of the proposed project.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

Not Applicable.

Revisions

For Revisions, the committee will consider the
appropriateness of the proposed expansion of the scope of the project. If the
Revision application relates to a specific line of investigation presented in
the original application that was not recommended for approval by the committee,
then the committee will consider whether the responses to comments from the
previous scientific review group are adequate and whether substantial changes
are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the NIAMS, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact/priority
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds
with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of
review by the National Arthritis and Musculoskeletal and Skin Diseases Advisory
Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and
welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.